The present invention relates to controlled release unit dose formulations of pharmaceuticals. In the prior art, many techniques have been used to provide controlled and extended-release pharmaceutical dosage forms in order to maintain therapeutic serum levels of medicaments and to minimize the effects of missed doses of drugs caused by a lack of patient compliance.
In the prior art, extended release tablets containing the calcium channel blocker nifedipine have been described which were based on the use of a rapid release core component that was covered by a secondary layer which contained nifedipine in a form which released the nifedipine at a slower rate than the core. The rapid release core is described as being capable of releasing at least 75% of the active drug in not less than one hour in a medium of 0.5% sodium lauryl sulfate/0.1N HCl. A product of this type is sold commercially as Adalat CC.RTM.. U.S. Pat. No. 4,892,741 discloses a press coated tablet for administering nifedipine. The core of this tablet contains a rapid release form of nifedipine and the outer coat around the core contains a dihydropyridine in slow release form.
Other extended release nifedipine dosage forms have been described in which the core is divided into two layers (compositions) one of which contains the active drug and the other contains a push layer of pharmacologically inactive ingredients which are osmotically active in the presence of gastrointestinal fluids. An outer water permeable coating covers the tablet which is provided with an aperture that is formed by laser drilled orifice to allow the medicament to be extruded out of the drug layer. A product of this type is disclosed in U.S. Pat. Nos. 4,783,337; 4,765,989; 4,612,008; and 4,327,725 and is sold commercially as Procardia XL.RTM.. Other controlled release compositions include those described in U.S. Pat. No. 3,948,254 and U.S. Pat. No. 4,036,227.
The osmotic dosage forms that are disclosed in U.S. Pat. No. 4,783,337 are described as having a passageway which includes an aperture, orifice, hole, porous element, hollow fiber, capillary tube, microporous insert, pore, microporous overlay or bore which extends through the semipermeable lamina wall into a drug layer. The patent also states that the passageway may be formed by mechanical drilling, laser drilling, eroding an erodible element, extracting, dissolving, bursting or leaching a passageway-former from the wall of the osmotic dosage form (col. 14, line 35 et seq.) which are pre-formed in the tablet during the manufacturing process. The only exemplified technique of forming a passageway in U.S. Pat. No. 4,783,337 is the use of a laser to drill a hole in the outer layer of the tablet and the dosage forms are all based on a drug layer superimposed on a secondary layer.
U.S. Pat. No. 4,285,987 describes an osmotic tablet which had a laser drilled aperture into the core of the tablet. The laser drilled hole was plugged with leachable sorbitol which was leached out in the presence of gastrointestinal fluid.
The present invention is concerned with providing a once a day tablet containing a calcium channel blocker tablet that does not have a rapid release core but is provided with a core having delayed release properties which contains an enteric coated calcium channel blocker compound which is prepared by mixing the calcium channel blocker with an enteric polymer in an aqueous medium and dispersing that mixture onto a solid pharmaceutical diluent to form a granulation.